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Infantile neuronal ceroid lipofuscinosis(INCL)

MedGen UID:
75666
Concept ID:
C0268281
Disease or Syndrome
Synonyms: INCL; SANTAVUORI DISEASE; SANTAVUORI-HALTIA DISEASE
SNOMED CT: Hagberg-Santavouri type neuronal ceroid lipofuscinosis (58258004); Polyunsaturated fatty acid lipidosis (58258004); Haltia-Santavouri type neuronal ceroid lipofuscinosis (58258004); Infantile neuronal ceroid lipofuscinosis (58258004); Hagberg-Santavuori disease (58258004); Polyunsaturated acid lipidosis (58258004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Monarch Initiative: MONDO:0019261
OMIM®: 256730
Orphanet: ORPHA79263

Definition

CLN1 disease is an inherited disorder that primarily affects the nervous system. Individuals with this condition have normal development in infancy, but typically by 18 months they become increasingly irritable and begin to lose previously acquired skills (developmental regression). In affected children, nerve cells in the brain die over time, leading to an overall loss of brain tissue (brain atrophy) and an unusually small head (microcephaly). Children with CLN1 disease have decreased muscle tone (hypotonia), intellectual and motor disability, and rarely are able to speak or walk. Some affected children develop repetitive hand movements. By age 2, individuals with this condition often have muscle twitches (myoclonus), recurrent seizures (epilepsy), and vision loss. Some affected children develop frequent respiratory infections. As the condition worsens, children have severe feeding difficulties that often require a feeding tube. Children with CLN1 disease usually do not survive past childhood.

Some people with CLN1 disease do not develop symptoms until later in childhood or in adulthood. As with younger affected children, older individuals develop a decline in intellectual function, myoclonus, epilepsy, and vision loss. In these individuals, life expectancy depends on when signs and symptoms of CLN1 disease develop and their severity; affected individuals may survive only into adolescence or through adulthood. Adults with CLN1 disease may also have movement disorders, including impaired muscle coordination (ataxia) or a pattern of movement abnormalities known as parkinsonism.

CLN1 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Augustine EF, Adams HR, de Los Reyes E, Drago K, Frazier M, Guelbert N, Laine M, Levin T, Mink JW, Nickel M, Peifer D, Schulz A, Simonati A, Topcu M, Turunen JA, Williams R, Wirrell EC, King S
Pediatr Neurol 2021 Jul;120:38-51. Epub 2021 Apr 9 doi: 10.1016/j.pediatrneurol.2021.04.002. PMID: 34000449
Williams RE, Adams HR, Blohm M, Cohen-Pfeffer JL, de Los Reyes E, Denecke J, Drago K, Fairhurst C, Frazier M, Guelbert N, Kiss S, Kofler A, Lawson JA, Lehwald L, Leung MA, Mikhaylova S, Mink JW, Nickel M, Shediac R, Sims K, Specchio N, Topcu M, von Löbbecke I, West A, Zernikow B, Schulz A
Pediatr Neurol 2017 Apr;69:102-112. Epub 2017 Feb 4 doi: 10.1016/j.pediatrneurol.2017.01.034. PMID: 28335910
Holmberg V, Lauronen L, Autti T, Santavuori P, Savukoski M, Uvebrant P, Hofman I, Peltonen L, Järvelä I
Neurology 2000 Aug 22;55(4):579-81. doi: 10.1212/wnl.55.4.579. PMID: 10953198

Recent clinical studies

Etiology

Beltrán L, Valenzuela GR, Loos M, Vargas R, Lizama R, Spinsanti P, Caraballo R
Epilepsy Res 2018 Aug;144:49-52. Epub 2018 May 16 doi: 10.1016/j.eplepsyres.2018.05.005. PMID: 29778029
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Järvelä I, Savukoski M, Ammälä P, von Koskull H
Prenat Diagn 1998 Nov;18(11):1169-73. PMID: 9854727
Soyombo AA, Hofmann SL
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Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Diagnosis

Chaves-Carballo E
J Child Neurol 2005 Mar;20(3):226-9. doi: 10.1177/08830738050200031001. PMID: 15832613
Romppanen EL
Scand J Clin Lab Invest 2001 Apr;61(2):123-9. doi: 10.1080/00365510151097629. PMID: 11347979
Holmberg V, Lauronen L, Autti T, Santavuori P, Savukoski M, Uvebrant P, Hofman I, Peltonen L, Järvelä I
Neurology 2000 Aug 22;55(4):579-81. doi: 10.1212/wnl.55.4.579. PMID: 10953198
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551
Baumann RJ, Markesbery WR
Neurology 1982 Nov;32(11):1277-81. doi: 10.1212/wnl.32.11.1277. PMID: 6890163

Therapy

Fyke Z, Johansson R, Scott AI, Wiley D, Chelsky D, Zak JD, Al Nakouzi N, Koster KP, Yoshii A
Mol Genet Metab 2024 Sep-Oct;143(1-2):108537. Epub 2024 Jul 15 doi: 10.1016/j.ymgme.2024.108537. PMID: 39033629Free PMC Article
Gutić M, Milosavljević MN, Safiye T, Milidrag A, Jankovic SM
Expert Rev Pharmacoecon Outcomes Res 2023 Jun;23(5):561-570. Epub 2023 Apr 3 doi: 10.1080/14737167.2023.2197213. PMID: 36994735
Lewis G, Morrill AM, Conway-Allen SL, Kim B
J Child Neurol 2020 Apr;35(5):348-353. Epub 2019 Dec 29 doi: 10.1177/0883073819895694. PMID: 31884868
Baker EH, Levin SW, Zhang Z, Mukherjee AB
AJNR Am J Neuroradiol 2017 Feb;38(2):376-382. Epub 2016 Oct 20 doi: 10.3174/ajnr.A4978. PMID: 27765741Free PMC Article
Kohlschütter A, Schulz A
Pediatr Endocrinol Rev 2016 Jun;13 Suppl 1:682-8. PMID: 27491216

Prognosis

Augustine EF, Adams HR, de Los Reyes E, Drago K, Frazier M, Guelbert N, Laine M, Levin T, Mink JW, Nickel M, Peifer D, Schulz A, Simonati A, Topcu M, Turunen JA, Williams R, Wirrell EC, King S
Pediatr Neurol 2021 Jul;120:38-51. Epub 2021 Apr 9 doi: 10.1016/j.pediatrneurol.2021.04.002. PMID: 34000449
Baker EH, Levin SW, Zhang Z, Mukherjee AB
AJNR Am J Neuroradiol 2017 Feb;38(2):376-382. Epub 2016 Oct 20 doi: 10.3174/ajnr.A4978. PMID: 27765741Free PMC Article
Kurze AK, Galliciotti G, Heine C, Mole SE, Quitsch A, Braulke T
Hum Mutat 2010 Feb;31(2):E1163-74. doi: 10.1002/humu.21184. PMID: 20020536
Holmberg V, Lauronen L, Autti T, Santavuori P, Savukoski M, Uvebrant P, Hofman I, Peltonen L, Järvelä I
Neurology 2000 Aug 22;55(4):579-81. doi: 10.1212/wnl.55.4.579. PMID: 10953198
Varilo T, Savukoski M, Norio R, Santavuori P, Peltonen L, Järvelä I
Am J Hum Genet 1996 Mar;58(3):506-12. PMID: 8644710Free PMC Article

Clinical prediction guides

O'Neal M, Noher de Halac I, Aylward SC, Yildiz V, Zapanta B, Abreu N, de Los Reyes E
Pediatr Neurol 2024 May;154:51-57. Epub 2024 Mar 1 doi: 10.1016/j.pediatrneurol.2024.02.010. PMID: 38531163
Collier AM, Nemtsova Y, Kuber N, Banach-Petrosky W, Modak A, Sleat DE, Nanda V, Lobel P
Biochem J 2020 Feb 14;477(3):727-745. doi: 10.1042/BCJ20190874. PMID: 31957806Free PMC Article
Kurze AK, Galliciotti G, Heine C, Mole SE, Quitsch A, Braulke T
Hum Mutat 2010 Feb;31(2):E1163-74. doi: 10.1002/humu.21184. PMID: 20020536
Holmberg V, Lauronen L, Autti T, Santavuori P, Savukoski M, Uvebrant P, Hofman I, Peltonen L, Järvelä I
Neurology 2000 Aug 22;55(4):579-81. doi: 10.1212/wnl.55.4.579. PMID: 10953198
Varilo T, Savukoski M, Norio R, Santavuori P, Peltonen L, Järvelä I
Am J Hum Genet 1996 Mar;58(3):506-12. PMID: 8644710Free PMC Article

Recent systematic reviews

Chen ZR, Liu DT, Meng H, Liu L, Bian WJ, Liu XR, Zhu WW, He Y, Wang J, Tang B, Su T, Yi YH
Seizure 2019 Jul;69:180-185. Epub 2018 Sep 2 doi: 10.1016/j.seizure.2018.08.027. PMID: 31059981

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